Blesa Rafael, Davidson Michael, Kurz Alexander, Reichman William, van Baelen Bart, Schwalen Susanne
Hospital Clinic Universitari, Barcelona, Spain.
Dement Geriatr Cogn Disord. 2003;15(2):79-87. doi: 10.1159/000067974.
Galantamine (Reminyl), a novel agent with a dual mode of action, modulates nicotinic acetylcholine receptors and inhibits acetylcholinesterase. Galantamine has consistently demonstrated a broad range of beneficial effects and has shown sustained benefits in cognitive and functional abilities for at least 12 months in patients with mild-to-moderate Alzheimer's disease (AD). As pivotal studies demonstrating the efficacy of cholinergic drugs were designed to exclude patients with severer AD, many patients with the advanced stage of this condition are currently not treated due to the lack of demonstrated efficacy in clinical trials. We aimed to investigate whether there was any evidence for the benefits of galantamine in patients with severer disease, by performing a post hoc analysis using data extracted from the population of the two long-term galantamine studies. We evaluated the efficacy of galantamine in patients with 'advanced moderate' AD. 'Advanced moderate' patients were those with baseline Mini Mental State Examination (MMSE) scores </=14 or Alzheimer's Disease Assessment Scale - cognitive subscale (ADAS-cog) scores >30. These patients were compared with matched controls who received placebo in a different historical study. Cognitive abilities (assessed using the ADAS-cog scale) of 'advanced moderate' AD patients receiving galantamine for 12 months were maintained at baseline levels after 12 months, and significantly improved over those of placebo patients (p < 0.001). Of the 'advanced moderate' patients receiving galantamine, 51% with baseline ADAS-cog of >30 maintained or improved their ADAS-cog scores over baseline values, compared with 13% receiving placebo (p < 0.001). In the subgroup of 'advanced moderate' patients with baseline MMSE </=14, 48% of those receiving galantamine and 4% of those receiving placebo maintained or improved their ADAS-cog scores at 12 months (p = 0.001). In both subgroups, the treatment difference (galantamine vs. historical placebo) amounted to approximately 10 points on the ADAS-cog scale. Functional abilities, as assessed using the Disability Assessment for Dementia scale, remained significantly superior in galantamine-treated patients compared with historical placebo-treated patients at 12 months (p < 0.001). In conclusion, galantamine offered sustained efficacy to patients with 'advanced moderate' AD, confirming the benefits seen in published studies of patients with mild-to-moderate AD. This drug has potential for broader use in clinical practice.
加兰他敏（雷美替明）是一种具有双重作用模式的新型药物，可调节烟碱型乙酰胆碱受体并抑制乙酰胆碱酯酶。加兰他敏一直显示出广泛的有益效果，并且在轻度至中度阿尔茨海默病（AD）患者中，其认知和功能能力在至少12个月内持续受益。由于证明胆碱能药物疗效的关键研究旨在排除重度AD患者，因此目前许多处于该疾病晚期的患者因临床试验中缺乏已证明的疗效而未得到治疗。我们旨在通过对两项加兰他敏长期研究人群中提取的数据进行事后分析，调查加兰他敏对病情较重患者有益的证据。我们评估了加兰他敏对“重度中度”AD患者的疗效。“重度中度”患者是指基线简易精神状态检查表（MMSE）评分≤14或阿尔茨海默病评估量表 - 认知分量表（ADAS-cog）评分>30的患者。将这些患者与在另一项历史研究中接受安慰剂的匹配对照组进行比较。接受加兰他敏治疗12个月的“重度中度”AD患者的认知能力（使用ADAS-cog量表评估）在12个月后维持在基线水平，并且显著优于安慰剂组患者（p<0.001）。在接受加兰他敏治疗的“重度中度”患者中，基线ADAS-cog>30的患者中有51%的ADAS-cog评分维持或高于基线值，而接受安慰剂的患者为13%（p<0.001）。在基线MMSE≤14的“重度中度”患者亚组中，接受加兰他敏治疗的患者中有48%以及接受安慰剂治疗的患者中有4%在12个月时维持或提高了他们的ADAS-cog评分（p = 0.001）。在两个亚组中，治疗差异（加兰他敏与历史安慰剂相比）在ADAS-cog量表上约为10分。使用痴呆症残疾评估量表评估的功能能力在12个月时，加兰他敏治疗的患者与历史安慰剂治疗的患者相比仍显著更优（p<0.001）。总之，加兰他敏对“重度中度”AD患者具有持续疗效，证实了在轻度至中度AD患者已发表研究中所见的益处。这种药物在临床实践中有更广泛应用的潜力。
